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United States Patent | 5,733,899 |
Frye ,   et al. | March 31, 1998 |
A method of treating a bacterial or fungal infection in a patient by administering an effective amount of a compound of Formula (III): ##STR1## wherein, the substituents are as defined in the specification.
Inventors: | Frye; Leah L. (Ravena, NY); Zasloff; Michael A. (Merion Station, PA); Kinney; William A. (Churchill, PA); Moriarty; Robert (Oak Park, IL); Collins; Delwood C. (Lexington, KY) |
Assignee: | Magainin Pharmaceuticals Inc. (Plymouth Meeting, PA) |
Appl. No.: | 416883 |
Filed: | April 20, 1995 |
PCT Filed: | September 13, 1994 |
PCT NO: | PCT/US94/10265 |
371 Date: | April 20, 1995 |
102(e) Date: | April 20, 1995 |
PCT PUB.NO.: | WO95/24415 |
PCT PUB. Date: | September 14, 1995 |
Current U.S. Class: | 514/169; 514/172; 514/176; 514/182 |
Intern'l Class: | A61K 031/56; A61K 031/58 |
Field of Search: | 514/169,170,171,172,173,174,175,176,177,178,179,180,181,182 |
3016390 | Jan., 1962 | Counsell. | |
3370070 | Feb., 1968 | Klimstra et al. | |
4220598 | Sep., 1980 | Hixson, Jr. et al. | 424/1. |
4372888 | Feb., 1983 | Hjelmeland | 260/397. |
4425273 | Jan., 1984 | Iida et al. | 262/397. |
4514393 | Apr., 1985 | Castagnola et al. | 260/397. |
4545938 | Oct., 1985 | Mosbach et al. | 260/397. |
4550163 | Oct., 1985 | Voss et al. | 544/244. |
4565811 | Jan., 1986 | DiSchiena | 514/182. |
4771042 | Sep., 1988 | Braughler et al. | |
4793948 | Dec., 1988 | Hatono et al. | 260/397. |
4966897 | Oct., 1990 | Angelastro et al. | 514/177. |
4994443 | Feb., 1991 | Folkman et al. | |
5001116 | Mar., 1991 | Folkman et al. | |
5004737 | Apr., 1991 | Kim et al. | |
5039529 | Aug., 1991 | Bergendal et al. | |
5057509 | Oct., 1991 | Pellicciari et al. | 514/182. |
5061701 | Oct., 1991 | Pellicciari et al. | 514/182. |
5063222 | Nov., 1991 | Komoto et al. | 514/180. |
5075464 | Dec., 1991 | Blohm et al. | 552/522. |
5135919 | Aug., 1992 | Folkman et al. | |
5192756 | Mar., 1993 | Zasloff et al. | |
5250524 | Oct., 1993 | Kramer et al. | |
Foreign Patent Documents | |||
0394971 | Oct., 1990 | EP. | |
0466315 | Jan., 1992 | EP. | |
2361899 | Mar., 1978 | FR. | |
1565351 | Apr., 1980 | GB. | |
WO 87/02367 | Apr., 1987 | WO. | |
WO 91/19731 | Dec., 1991 | WO. | |
WO 93/25197 | Dec., 1993 | WO. | |
WO 94/20520 | Sep., 1994 | WO. | |
WO 94/19366 | Sep., 1994 | WO. |
Moriarty, R.M., et al., "Synthesis of Squalamine. A Steroidal Antibiotic from the Shark," Tetrahedron Letters, vol. 35, No. 44, 31 Oct. 1994, pp. 8103-8106. K.S. Moore et al., "Squalamine: An aminosterol antibiotic from the shark," Proc. Natl. Acad. Sci. USA, vol. 90, Feb. 1993, pp. 1354-1358. A.M. Bellini et al., "Antimicrobial Activity of Basic Cholane Derivatives Part IX," Arch. Pharm. (Weinheim), vol. 323, 1990, pp. 201-205. A.M. Bellini et al., "Antimicrobial activity of basic cholane derivatives X," Steroids, vol. 56, Jul. 1991, pp. 395-397. J. McKenna et al., "Bis-steroids as Potential Enzyme Models," J.C.S. Chem. Comm., 1977, pp. 809-811. S.L. Wehrli et al., "Structure of the novel steroidal antibiotic squalamine determined by two-dimensional NMR spectroscopy," Steroids, vol. 58, No. 8, Aug. 1993. A. Sadownik et al., "Rapid Construction of a Squalamine Mimic," Journal of the American Chemical Society, vol. 117, 1995, pp. 6138-6139. R. Crum et al., "A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment," Science, vol. 230, Dec. 20, 1985, pp. 1377-1378. W. Auerbach et al., "Angiogenesis Inhibition: A Review," Pharmac. Ther., vol. 63, 1994, pp. 265-311. A. Gagliardi et al., "Inhibition of Angiogenesis by Antiestrogens," Cancer Research, vol. 53, Feb. 1, 1993, pp. 533-535. |
TABLE ______________________________________ MIC values (.mu.g/ml) Compound S. aureus E. coli P. aeruginosa C. albicans ______________________________________ 303# 8 128-256 128 256 304# 2-4 128 128 128 318@ 128 32 64 >256 319@ 128 64 64 >256 328# 8-16 64 128 64 343# 4-16 32 128 64 351.sup..dagger. 16 >256 >256 >256 352.sup..dagger. 4 >256 >256 64 squalamine* 0.5-1 2-4 16 8 ______________________________________ Notes: @ -- as free base; # -- as 3HCl salt; .sup..dagger. -- as 2HCl salt; * -- reference standard, as 2HClTFA salt, prepared from shark liver.